Tooth Bleaching Compositions

ABSTRACT

The present invention relates to improved dental compositions and methods for bleaching teeth. More specifically, this invention is directed towards hydrogen peroxide-containing compounds that are maintained at a substantially constant pH range of 6.0-10.0 during the tooth-bleaching procedure in the presence of a calcium chelating agent.

RELATED U.S. APPLICATION(S)

This application is a continuation of U.S. patent application Ser. No.11/485,726, filed on Jul. 13, 2006, which is a continuation of U.S.application Ser. No. 10/219,965, filed Aug. 15, 2002, which is acontinuation of U.S. application Ser. No. 10/003,210, filed Oct. 31,2001, now U.S. Pat. No. 6,488,914, which is a continuation of U.S.application Ser. No. 09/192,609, filed on Nov. 16, 1998, now U.S. Pat.No. 6,331,292, which was a continuation of U.S. application Ser. No.08/719,569, filed on Sep. 25, 1996, now U.S. Pat. No. 5,922,307, whichclaimed benefit of U.S. Provisional Application Ser. No. 60/004,258,filed Sep. 25, 1995, all of which prior applications and patents areincorporated herein by reference.

TECHNICAL FIELD

The present invention relates to improved dental bleaching compositionsand methods for bleaching teeth.

BACKGROUND ART

White teeth have long been considered cosmetically desirable.Unfortunately, teeth become almost invariably discolored in the absenceof intervention. The tooth structures which are generally responsiblefor presenting a stained appearance are enamel, dentin, and the acquiredpellicle. Tooth enamel is predominantly formed from inorganic material,mostly in the form of hydroxyapatite crystals and further containsapproximately 5% organic material primarily in the form of collagen. Incontrast, dentin is composed of about 20% protein including collagen,the balance consisting of inorganic material, predominantlyhydroxyapatite crystals, similar to that found in enamel. The acquiredpellicle is a proteinaceous layer on the surface of tooth enamel whichreforms rapidly after an intensive tooth cleaning.

Staining of teeth results from extrinsic and/or intrinsic staining.Extrinsic staining of the acquired pellicle arises as a result ofcompounds such as tannins and polyphenolic compounds which becometrapped in and tightly bound to the proteinaceous layer on the surfaceof the teeth. This type of staining can usually be removed by mechanicalmethods of tooth cleaning. In contrast, intrinsic staining occurs whenstaining compounds penetrate the enamel and even the dentin or arisefrom sources within the tooth. This type of staining is not amenable tomechanical methods of tooth cleaning and chemical methods are required.

Consequently, tooth-bleaching compositions generally fall into twocategories: (1) gels, pastes, or liquids, including toothpastes that aremechanically agitated at the stained tooth surface in order to affecttooth stain removal through abrasive erosion of stained acquiredpellicle; and (2) gels, pastes, or liquids that accomplish thetooth-bleaching effect by a chemical process while in contact with thestained tooth surface for a specified period, after which theformulation is removed. In some cases, the mechanical process issupplemented by an auxiliary chemical process which may be oxidative orenzymatic.

The majority of professionally-monitored at-home tooth-bleachingcompositions act by oxidation. These compositions are dispensed directlyto a patient for use in a custom-made tooth-bleaching tray, held inplace in the mouth for contact times of greater than about 60 minutes,and sometimes as long as 8 to 12 hours. The slow rate of bleaching is inlarge part, the consequence of formulations that are developed tomaintain stability of the oxidizing composition. The most commonly usedoxidative compositions contain the hydrogen peroxide precursor carbamideperoxide which is mixed with an anhydrous or low-water content,hygroscopic viscous carrier containing glycerine and/or propylene glycoland/or polyethylene glycol. When contacted by water, carbamide peroxidedissociates into urea and hydrogen peroxide. Associated with the slowrate of bleaching in the hygroscopic carrier, the currently availabletooth-bleaching compositions cause tooth sensitization in over 50% ofpatients. Tooth sensitivity is believed to result from the movement offluid through the dentinal tubes toward nerve endings in the tooth. Thismovement is enhanced by the carriers for the carbamide peroxide. Infact, it has been determined that glycerine, propylene glycol andpolyethylene glycol can each give rise to varying amounts of toothsensitivity following exposure of the teeth to heat, cold, overly sweetsubstances, and other causative agents.

Prolonged exposure of teeth to bleaching compositions, as practiced atpresent, has a number of adverse effects in addition to that of toothsensitivity. These include: solubilization of calcium from the enamellayer at a pH less than 5.5 with associated demineralization;penetration of the intact enamel and dentin by the bleaching agents, soas to reach the pulp chamber of a vital tooth thereby risking damage topulpal tissue; and dilution of the bleaching compositions with salivawith resulting leaching from the dental tray and subsequent digestion.

The stability of existing formulations of hydrogen peroxide-containingtooth-bleaching compositions in terms of shelf-life as well as over theperiod of use in the mouth, depends, in general, or an acidic pH. Thehydrogen peroxide becomes markedly less stable as the pH increases.Indeed, Frysh, et al. (Journal of Esthetic Dentistry Vol. 7, No. 3, pp.130-133, 1995) described the use of high concentration (35%) of hydrogenperoxide solutions at an initial alkaline pH, which was required to beformulated immediately before use and was administered in the form of aliquid to extracted teeth to achieve tooth bleaching. Phillips andBowles (IADR Abstract J. Dent.res 75, 1996) have demonstrated thathydrogen peroxide penetrates the enamel of extracted teeth less readilyover a 15 minute period at pH 9.0 than at pH 4.5. Carbamide peroxidecompositions have been formulated at a pH of 5.0-6.5 using hygroscopiccarriers and maintaining a low water content. This type of formulationis problematic with regard to enhanced tooth sensitivity. On contactwith saliva, the water content of the formulation increases, causing thecarbamide to disassociate into urea and hydrogen peroxide and the pH tobe decreased. In fact, the equilibrium pH of a 10% carbamide peroxidesolution is approximately 3.45 and a typical commercially-availabletooth-bleaching gel with 10% carbamide peroxide when combined withsaliva in a 1:1 weight ratio has an initial pH of 5.6 and graduallydecreases to pH 4.8 after 8 hours.

Thus, currently available tooth-bleaching compositions that rely onhydrogen peroxide as oxidizing agents, all release hydrogen peroxidefrom precursors at low pH levels despite the low rates oftooth-bleaching activity.

There is a need for a home use tooth-bleaching product that is stable,easy to use, and rapid-acting that utilizes reduced amounts of hydrogenperoxide and is capable of administration to a patient by means of adental tray. There is a further need for a tooth-bleaching compositionthat may reduce hand soft tissue irritation, tooth sensitivity, andbleaching composition ingestion to further increase patient compliance.

SUMMARY OF THE INVENTION

The invention satisfies the above needs. An embodiment of the inventionincludes a tooth-bleaching composition for contacting a tooth surface ina subject that includes a hydrogen peroxide-containing compound.Furthermore the composition includes a matrix for administering thehydrogen peroxide-containing compound to the tooth surface. The matrixcomprises a thickening agent, an agent for stabilizing the hydrogenperoxide-containing compound, a pH adjusting agent and a calciumchelating agent, wherein the pH of the tooth-bleaching compositionduring the bleaching process is substantially constant with a range ofpH 6.0-10.

A further embodiment of the invention includes a dosage delivery unitfor tooth bleaching, including a multi-chamber vessel wherein eachchamber is responsive to an applied pressure from an external source,such that a mixture of reagents contained within a compartment includinga hydrogen peroxide containing composition and a matrix, will be forcedto exit the compartment through a mixing baffle in response to theexternally applied pressure.

A further embodiment of the invention includes a method for bleachingteeth including preparing a composition as described above andadministering the composition to the tooth surface.

DETAILED DESCRIPTION OF THE INVENTION

The present invention comprises compositions and methods for bleachingtooth enamel in situ which allow the use of reduced concentrations ofhydrogen peroxide in tooth-bleaching compositions in order to achieveeffective tooth bleaching in a contact time of less than one hour.

The tooth surface is defined here and in the claims as a portion of atooth which is directly responsible for the stained appearance of saidtooth. The term tooth surface generally means a tooth's acquiredpellicle, plaque, enamel, and combinations thereof.

The matrix is defined here and in the claims as the gel, paste, orliquid in which the hydrogen peroxide containing compound is placed foradministration to the subject.

The subject referred to here and in the claims is commonly a humansubject but also includes domestic animals.

An important aspect of the present invention is the finding that theefficiency of the bleaching reaction in a tooth using a chemicaltooth-bleaching agent such as hydrogen peroxide can be significantlyenhanced at a pH greater than 5.5, more particularly a pH in the rangeof 6-10, for example in a range of pH of 7-10, more particularly between8.0 and 9.5, providing that the pH is maintained at a substantiallyconstant range throughout the tooth-bleaching process and a calciumchelating agent is included in the composition to prevent precipitationof calcium ions. (Table 1-4)

Suitable pH adjusting agents include, but are not limited to, sodiumhydroxide, potassium hydroxide, ammonium hydroxide, sodium carbonate,potassium carbonate, TRIS and triethanolamine.

Examples of calcium chelating agents include any of the calciumchelating agents known in the art. Examples include EDTA and its salts,citric acid and its salts, gluconic acid and its salts, alkali metalpyrophosphates and alkali metal polyphosphates. The use of citric acid,sodium acid pyrophosphates and disodium EDTA are shown in Table 1 andTable 2. The biological efficacy of sodium acid pyrophosphate is shownin Table 4. Without being bound to any particular theory, it is proposedthat calcium precipitation in the form of calcium phosphates arise inthe intercrystalline interstices of the tooth at elevated pHs and thisgives rise to a blockage of movement of the peroxide into the tooth withresulting negative effect on tooth bleaching. Calcium chelating agentsmay prevent this precipitation of calcium ions with the associatedobserved improvement of tooth-bleaching effect.

The composition may also contain a stabilizing agent for removing fromsolution, metal ions that interfere with the action of the hydrogenperoxide. In certain formulations, a single component may act either asa calcium chelating agent or as a stabilizing agent or may serve bothfunctions.

The ability to maintain constant pH range above 5.5 throughout theperiod of tooth bleaching coupled with the inhibition of calciumprecipitation that normally occurs at pH levels above 5.5, has resultedin a formulation that is suitable for use in the home and is capable ofachieving detectable tooth bleaching in less than 30 minutes.Furthermore, multiple treatments (each treatment lasting no longer than30 minutes) have been demonstrated to substantially whiten teeth(Example 5). In Example 5, 14 treatments using the inventiveformulation, were administered for twenty minutes, twice a day, overseven days. A mean ΔE of 7.32 was observed denoting a substantialtooth-bleaching effect compared with a ΔE of 4.73 using a prior artformulation for a period of time that was three times longer than thatof the novel formulation.

According to the invention, additional agents having tooth-bleachingeffect may be used to achieve detectable tooth bleaching in less than 30minutes. For example, sodium percarbonate has been demonstrated to bevery effective at tooth bleaching when maintained at a pH that isgreater than 5.5, more preferably in the range of 7-10, moreparticularly 8-9.5 that includes a calcium chelating agent. Thiscomposition differs from carbamide peroxide in that there is noacidification of that solution that results upon its dissociation.Consequently, the reagent may be maintained at a constant elevated pHfor an extended period of time without the necessity for addingbuffering reagents beyond that naturally supplied in the saliva. Unlikecarbamide peroxide, however the percarbonate is prepared in aformulation that does not include glycerine and is only slowly permeatedby water whereupon hydrogen peroxide is released. For this reason, itmay be desirable, but is not essential, to prepare the percarbonate in atwo-component composition, the two components being mixed before use soas to accelerate the tooth-bleaching effect (Examples 1 and 2).Formulations containing two components may be applied to the dental trayby squeezing a tube in much the same way as a single component. Themixing of the two components can be readily achieved using amulti-component tube containing a baffle, otherwise known in the art asa static mixer such that on squeezing the tube, material from each ofthe compartments is forced through the static mixer and are mixedtogether before emerging from single exit in the tube.

The present invention has important health benefits that follow fromshorter contact times of the tooth with hydrogen peroxide as well as theneed for lower concentrations of peroxide to achieve a desiredtooth-bleaching effect.

EXAMPLE 1 Composition of a Stable Tooth-Bleaching Formulation Suitablefor Use in a One Component System

The formulations below utilized ultrapure components to avoiddestabilization caused by metal ion contaminants. The chelating agentused here is one of disodium EDTA (1C) citric acid (1B), and sodium acidpyrophosphate (1F). The pH is modified using one of sodium hydroxidemonohydrate (1A, 1B, 1C), ammonium hydroxide (1F,1G),Tris(hydroxymethyl)aminomethane (1D), and triethanolamine (1E). Carbopolis a high molecular weight crosslinked polyacrylic acid thickeningagent. Hydrogen peroxide is used as the oxidizing agent.

TABLE 1 Example 1 A B C D E F G Ingredient WEIGHT PERCENT DistilledWater 86.41 86.21 86.31 72.80 79.52 86.50 73.81 1-Hydroxyethylidene-1,1-0.02 0.02 0.02 0.03 0.02 0.30 0.40 diphosphonic acid Sodium stannate0.02 0.02 0.02 0.03 0.02 0.05 0.05 trihydrate Citric Acid — 0.20 — — — —0.10 Calcium disodium EDTA — — 0.10 — — — — Sodium acid — — — — — 0.30 —pyrophosphate Hydrogen Peroxide 35% 10.30 10.30 10.30 17.14 17.14 8.6017.14 Carbopol 974P (B F 2.50 2.50 2.50 5.00 — 3.00 5.00 Goodrich)Carbopol 934P (B F — — — — 2.00 — — Goodrich) Sodium Hydroxide to pH 7.0to pH 7.0 to pH 7.0 — — — — Monohydrate Ammonium hydroxide — — — — — topH 6.5 to pH 8.5 28% Tris(hydroxymethyl) — — — to pH 8.0 — — —aminomethane Triethanolamine — — — — to pH 6.0 — — Total 100 100 100 100100 100 100 pH @ 25 deg. C. 7.0 7.0 7.0 8.0 6.0 6.5 8.5

The above formulations were prepared by dissolving the stabilizers1-hydroxyethylidene-1,1-diphosphonic acid and the sodium stannatetrihydrate in the distilled water using a Kynar-coated propeller-typeagitator (reserving enough water, if necessary, to dissolve theneutralizer in the final step). The hydrogen peroxide was then addedslowly to this mixture. The Carbopol 974P was then added to thedistilled, water/stabilizer/hydrogen peroxide mixture slowly while avortex was formed with the agitator blade. This dispersion was thenplaced in a Kynar-coated vacuum double planetary mixer to which the pHadjusting agent was added slowly to affect neutralization of theCarbopol 974P and to adjust the final composition pH. The resultingcomposition was a transparent viscous gel and was packaged infoil/plastic laminate tubes having a polyethylene product contact liner.

EXAMPLE 2 A Two Component Alkaline Tooth-Bleaching Formulation

A hydrogen peroxide-releasing composition was formulated which utilizedsodium percarbonate in an anhydrous gel, and was designed to be combinedwith a separate aqueous gel prior to use in order to dissolve the sodiumpercarbonate to form hydrogen peroxide and sodium carbonate. The pH ofthis composition, shown in Table 2, when combined in a volume ratio of 1to 1, was 9.0. The chelating agents used here are EDTA and sodium acidpyrophosphate.

TABLE 2 EXAMPLE 2 PART A PART B INGREDIENT WEIGHT PERCENT DistilledWater — 95.20 Polyethylene glycol 400 83.00 — Sodium percarbonate(powder) 12.00 — EDTA — 0.20 Sodium acid pyrophosphate — 0.30 Carbopol974P (Goodrich) 2.50 4.00 Sodium Hydroxide Monohydrate — to pH 7.0Tris(hydroxymethyl)aminomethane 2.50 — Total 100 100

The above composition parts were prepared as follows:

Part A—The Carbopol was dispersed in the polyethylene glycol using apropeller-type agitator with Kynar-coated product contact surfaces. Theresulting dispersion was added to a Kynar-coated vacuum double planetarymixer (as in Example 1) and neutralized with thetris(hydroxymethyl)aminomethane under low shear mixing. To the resultantneutralized Carbopol gel, sodium percarbonate was added and disperseduntil the composition was a homogenous white paste.

Part B—The Carbopol was added to the water (in the EDTA and sodium acidpyrophosphate had already been dissolved) and agitated as above. Theresulting dispersion was transferred to the Kynar-coated vacuum doubleplanetary mixer and neutralized with the sodium hydroxide monohydrateunder low shear mixing. The final gel was clear and viscous, with a pHof around 7.0.

EXAMPLE 3 Preparation of a Tooth-Bleaching Formulation Having Acidic pH

In order to demonstrate the superior ability of the inventive hydrogenperoxide gel composition of Examples 1 and 2 to bleach teeth, acomposition was prepared which was similar to that of Example 1E, exceptthat the pH was adjusted to 4.5.

TABLE 3 INGREDIENT PERCENT Distilled water 79.821-Hydroxyethylidene-1,1-diphosphonic acid 0.02 Sodium stannatetrihydrate 0.02 Carbopol 974P 2.00 Hydrogen Peroxide 35% 17.14Triethanolamine 1.00 TOTAL 100.00

The formula was prepared as in Example 1, resulting in viscous gel witha pH of approximately 4.5. The formulation is similar to 1E, thedifference lying in the pH of the composition.

EXAMPLE 4 Assay to Determine Tooth Bleaching

Bovine incisors, which had been imbedded in an acrylic matrix such thatthe buccal surfaces presented themselves on the top surface, werestained in a manner to duplicate the tooth staining observed in vivo byhumans (alternately exposed to air and a staining broth at 37 degrees C.containing typticase soy broth, tea, coffee, mucin, FeCl₃ and Sarcinalutea, for a period of about four days). Each stained bovine incisor wasnumbered and measured for degree of staining (color by the CIELABprotocol) with a Minolta 5031 Spectrophotometer (3 mm aperture, 8exposure averaging, outliers discarded.). Incisors were covered withdifferent tooth-bleaching compositions in the tables above, in additionto a commercially available carbamide peroxide composition (Opalescence10% Carbamide Peroxide Gel, Ultradent, South Jordan, Utah). All gelswere kept in contact with the incisor surface for exactly 15 minutes,whereupon the tooth was rinsed clean of any gel residue with distilledwater and swabbed with saliva. The degree of stain removal wasthereafter immediately determined by measuring the incisor surface, asabove, for color, and the change in tooth color recorded below as ΔE.Absolute color change is defined as the square root of the sum of thesquares of all color components (L, a, and b).

√{square root over ([(ΔL)²+(Δa)²+(Δb)²])}{square root over([(ΔL)²+(Δa)²+(Δb)²])}{square root over ([(ΔL)²+(Δa)²+(Δb)²])}=ΔE

TABLE 4 pH Initial Color Final Color Tooth # Product/Example (neat) L ab L a b ΔE 1 Opalescence 6.5 41.79 3.17 11.78 44.29 2.96 11.70 2.51 2Example 3 4.5 39.84 4.99 12.00 43.96 4.47 10.94 4.29 3 1E 6.0 40.44 4.419.53 46.32 3.48 7.54 6.27 4 1A 7.0 36.02 3.84 10.10 42.57 2.59 8.28 6.915 1B 7.0 38.81 3.98 11.38 45.92 2.38 8.81 7.73 6 1C 7.0 36.90 4.05 12.6144.11 2.45 10.53 7.67 7 1D 8.0 41.55 3.67 10.51 49.77 1.26 7.82 8.98 81F 6.5 38.55 5.01 10.87 44.78 3.67 9.50 6.52 9 1G 8.5 40.26 4.59 9.9348.28 3.13 7.97 8.38 10 Example 2 9.0 36.49 4.00 12.64 44.93 2.20 10.638.78

This table shows the effect of pH on tooth bleaching. As shown for tooth#2 with the formulation of Example 3 and tooth #3 treated with theformulation of 1E in Example 1, the increase in pH from 4.5 (2) to6.0(3) results in an increased ΔE from 4.29 to 6.27.

The table further shows the positive effect of the calcium chelatingagent on tooth bleaching. For example, for 1A, 1B, and 1C (all at pH7.0), 1A lacked a calcium chelating agent whereas 1B and 1C contained achelating agent. There was an observed improvement in ΔE in the presenceof the chelating agent. The best tooth-bleaching results were obtainedat the highest pH, namely, in this experiment, pH 8.0 and pH 9.0.

Opalescence is a commercial product which has been pH adjusted to pH 6.5before use but shows a poor performance with regard to color change overtime of the experiment. It is proposed that the pH of the formulation islowered as hydrogen peroxide and urea is released following dissociationof carbamide peroxide.

EXAMPLE 5 In Vivo Demonstration of Tooth Bleaching

Six volunteers aged 25 to 43 were separated into two groups of two andcustom dental trays were fashioned for each participant.

One group was given an unmarked 2 oz. tube containing the composition ofExample 1B and instructed to place a small amount of tooth-bleachingmaterial into the tray, position the tray over the teeth, and leave thetray in place for 20 minutes. Patients were instructed to repeated thisprocedure twice a day for one week, for a total of 14 treatments and 280minutes total tooth whitener exposure time.

The second group was given an unmarked 2 oz. tube of Opalescence 10%Carbamide Peroxide tooth-bleaching gel and instructed as above, with theexception of the duration of the bleaching procedure twice a day for oneweek, for a total of 14 treatments and 840 minutes total tooth-bleachingexposure time.

The results of direct tooth surface (upper left central incisor) colormeasurements, both before and after treatment (as in Example 5 above),are recorded in the Table 5 below.

TABLE 5 Treatment Initial Color Final Color Tooth # Product/Example Time(minutes) L a b L a b ΔE 1 1B 280 53.76 4.65 11.65 60.34 0.97 8.80 8.062 1B 280 49.42 2.97 9.48 56.99 0.46 7.38 8.25 3 1B 280 51.26 2.33 8.2555.63 0.87 4.99 5.65 4 Opalescence 840 52.78 1.75 6.14 57.26 1.42 2.106.04 5 Opalescence 840 56.35 1.79 5.21 59.13 0.65 2.44 4.09 6Opalescence 840 55.71 2.72 7.10 58.60 1.09 4.75 4.07

The average ΔE for the Example 1B group was 7.32, whereas the average ΔEfor the Opalescence group was 4.73. The present inventive compositionsare thus shown to offer a substantially improved degree of toothbleaching in a shorter exposure time than a prior art composition.

1-14. (canceled)
 15. A tooth bleaching composition comprising: hydrogenperoxide, and a matrix for carrying the hydrogen peroxide, the matrixhaving a water content of at least 75% by weight, based on the weight ofthe composition, a concentration of high molecular weight crosslinkedpolyacrylic acid of between approximately 2.0% and approximately 5.0% byweight, based on the weight of the composition, an alkaline pH adjustingagent, and a concentration of a stabilizing agent selected from thegroup consisting of sodium stannate trihydrate,1-Hydroxyethylidene-1,1-diphosphonic acid, and combinations thereof, ofbetween approximately 0.02% and approximately 0.5% by weight, based onthe weight of the composition, wherein the pH of the composition duringthe bleaching process is substantially constant within a range ofbetween approximately 6.0 and approximately 10.0.
 16. A compositionaccording to claim 15, wherein the concentration of hydrogen peroxide inthe composition is less than 15% by weight of the composition.
 17. Acomposition according to claim 15, wherein the matrix is sufficientlypure in order to avoid peroxide destabilization by metal ioncontaminants, so as to permit packaging as a one-component system.
 18. Acomposition according to claim 15, wherein the pH of the compositionduring the bleaching process is substantially constant within a rangepreferred for use within an oral cavity of between approximately 6.0 andapproximately 8.0.
 19. A composition according to claim 15, wherein thematrix also has a concentration of a calcium chelating agent of betweenapproximately 0.02% and approximately 0.4% by weight, based on theweight of the composition.
 20. A composition according to claim 15,wherein the stabilizing agent may also act as a calcium chelating agent.